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Article ; Online: Stats: a trillion P values and counting.

Adams, Hieab H H

2019 Volume 569, Issue 7756, Page(s) 336

MeSH term(s)	Data Interpretation, Statistical ; Educational Measurement/methods ; Educational Measurement/standards ; Health Policy ; Humans ; Probability ; Reproducibility of Results
Language	English
Publishing date	2019-05-15
Publishing country	England
Document type	Letter
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/d41586-019-01527-6
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The Uncovering Neurodegenerative Insights Through Ethnic Diversity consortium.

Adams, Hieab H H / Evans, Tavia E / Terzikhan, Natalie

The Lancet. Neurology

2019 Volume 18, Issue 10, Page(s) 915

MeSH term(s)	Brain/diagnostic imaging ; Brain Mapping ; Ethnic Groups/genetics ; Genetic Variation/genetics ; Genome-Wide Association Study ; Humans ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/ethnology ; Neurodegenerative Diseases/genetics ; Neuroimaging
Language	English
Publishing date	2019-09-13
Publishing country	England
Document type	Letter
ZDB-ID	2079704-7
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(19)30324-2
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Article ; Online: Genetic evidence for the most common risk factors for chronic axonal polyneuropathy in the general population.

Taams, Noor E / Knol, Maria J / Hanewinckel, Rens / Drenthen, Judith / Adams, Hieab H H / van Doorn, Pieter A / Ikram, Mohammad Arfan

European journal of neurology

2022 Volume 29, Issue 7, Page(s) 2066–2073

Abstract: Background and purpose: Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these ... ...

Abstract	Background and purpose: Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index [BMI], vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy. Methods: This study was performed within the population-based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6-78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome-wide association studies. Results: Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio [OR] Conclusions: This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well-known clinical risk factors and polyneuropathy.
MeSH term(s)	Aged ; Diabetes Mellitus, Type 2/complications ; Female ; Genome-Wide Association Study ; Humans ; Male ; Polyneuropathies/complications ; Polyneuropathies/epidemiology ; Polyneuropathies/genetics ; Risk Factors ; Vitamin B 12
Chemical Substances	Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2022-03-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15311
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Zs.A 4738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Neural correlates of orbital telorism.

Pawlak, Mikolaj A / Knol, Maria J / Vernooij, Meike W / Ikram, M Arfan / Adams, Hieab H H / Evans, T E

Cortex; a journal devoted to the study of the nervous system and behavior

2021 Volume 145, Page(s) 315–326

Abstract: Orbital telorism, the interocular distance, is clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known ... ...

Abstract	Orbital telorism, the interocular distance, is clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We derived measures of orbital telorism from cranial magnetic resonance imaging (MRI) by calculating the distance between the eyeball center of gravity in two population-based datasets (N = 5,653, N = 29,824; mean age 64.66, 63.75 years). This measure was found to be related to grey matter tissue density within numerous regions of the brain, including, but surprisingly not limited to, the frontal regions, in both positive and negative directions. Additionally, telorism was related to several cognitive functions, such as Purdue pegboard test (Beta, P-value (CI95%) -.02, 1.63 × 10
MeSH term(s)	Brain ; Cognition ; Frontal Lobe ; Gray Matter ; Humans ; Magnetic Resonance Imaging ; Neuropsychological Tests
Language	English
Publishing date	2021-10-22
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2021.10.003
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Article ; Online: Subcortical brain structures and the risk of dementia in the Rotterdam Study.

van der Velpen, Isabelle F / Vlasov, Vanja / Evans, Tavia E / Ikram, Mohammad Kamran / Gutman, Boris A / Roshchupkin, Gennady V / Adams, Hieab H / Vernooij, Meike W / Ikram, Mohammad Arfan

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 19, Issue 2, Page(s) 646–657

Abstract: Introduction: Volumetric and morphological changes in subcortical brain structures are present in persons with dementia, but it is unknown if these changes occur prior to diagnosis.: Methods: Between 2005 and 2016, 5522 Rotterdam Study participants ( ... ...

Abstract	Introduction: Volumetric and morphological changes in subcortical brain structures are present in persons with dementia, but it is unknown if these changes occur prior to diagnosis. Methods: Between 2005 and 2016, 5522 Rotterdam Study participants (mean age: 64.4) underwent cerebral magnetic resonance imaging (MRI) and were followed for development of dementia until 2018. Volume and shape measures were obtained for seven subcortical structures. Results: During 12 years of follow-up, 272 dementia cases occurred. Mean volumes of thalamus (hazard ratio [HR] per standard deviation [SD] decrease 1.94, 95% confidence interval [CI]: 1.55-2.43), amygdala (HR 1.66, 95% CI: 1.44-1.92), and hippocampus (HR 1.64, 95% CI: 1.43-1.88) were strongly associated with dementia risk. Associations for accumbens, pallidum, and caudate volumes were less pronounced. Shape analyses identified regional surface changes in the amygdala, limbic thalamus, and caudate. Discussion: Structure of the amygdala, thalamus, hippocampus, and caudate is associated with risk of dementia in a large population-based cohort of older adults.
MeSH term(s)	Humans ; Aged ; Middle Aged ; Brain/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging/methods ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Dementia/diagnostic imaging ; Dementia/epidemiology ; Dementia/pathology
Language	English
Publishing date	2022-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12690
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

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Article: Genetic Burden for Late-Life Neurodegenerative Disease and Its Association With Early-Life Lipids, Brain, Behavior, and Cognition.

Lamballais, Sander / Muetzel, Ryan L / Ikram, Mohammad Arfan / Tiemeier, Henning / Vernooij, Meike W / White, Tonya / Adams, Hieab H H

Frontiers in psychiatry

2020 Volume 11, Page(s) 33

Abstract: Background: Genetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced ... ...

Abstract	Background: Genetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced back decades before the onset of disease symptoms. Previous studies have shown evidence for plausible links of apolipoprotein E (APOE), the most important genetic marker for Alzheimer's disease, with early-life cognition and neuroimaging markers. We aimed to assess whether genome-wide genetic burden for the aforementioned neurodegenerative diseases plays a role in early-life processes. Methods: We studied children from the Generation R Study, a prospective birth cohort. APOE genotypes and polygenic genetic burdens for Alzheimer's disease, Parkinson's disease, and frontotemporal dementia were obtained through genome-wide genotyping. Non-verbal intelligence was assessed through cognitive tests at the research center around the age of 6 years, and educational attainment through a national school performance test around the age of 11 years. The Child Behavior Checklist was administered around the age of 10 years, and data from the anxious/depressed, withdrawn/depressed, and the internalizing behavior problems scales were used. Children participated in a neuroimaging study when they were 10 years old, in which structural brain metrics were obtained. Lipid serum profiles, which may be influenced by APOE genotype, were assessed from venal blood obtained around the age of 6 years. The sample size per analysis varied between 1,641 and 3,650 children due to completeness of data. Results: We did not find evidence that APOE genotype or the polygenic scores impact on childhood nonverbal intelligence, educational attainment, internalizing behavior, and global brain structural measures including total brain volume and whole brain fractional anisotropy (all p > 0.05). Carriership of the APOE ε2 allele was associated with lower and APOE ε4 with higher low-density lipoprotein cholesterol concentrations when compared to APOE ε3/ε3 carriers. Conclusion: We found no evidence that genetic burden for late-life neurodegenerative diseases associates with early-life cognition, internalizing behavior, or global brain structure.
Language	English
Publishing date	2020-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2020.00033
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Article: Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood.

Vilor-Tejedor, Natalia / Ikram, Mohammad Arfan / Roshchupkin, Gennady / Vinke, Elisabeth J / Vernooij, Meike W / Adams, Hieab H H

Frontiers in psychiatry

2020 Volume 11, Page(s) 574

Abstract: Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about ...

Abstract	Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adulthood. Methods: Participant of the study were drawn from a population-based sample of 3,220 healthy individuals drawn from the Rotterdam Study, with at least two magnetic resonance imaging (MRI)-scans (8,468 scans) obtained every 3-4 years. We investigate associations of genetic single nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies for ADHD, and trajectories of global and subcortical brain structures in an adult population (aged 50 years and older), acquired through MRI. We also evaluated the existence of age-dependent effects of these genetic variants on trajectories of brain structures. These analyses were reproduced among individuals 70 years of age or older to further explore aging-dependent mechanisms. We additionally tested baseline associations using the first MRI-scan of the 3,220 individuals. Results: We observed significant age-dependent effects on the rs212178 in trajectories of ventricular size (lateral ventricles, P= 4E-05; inferior lateral ventricles, P=3.8E-03; third ventricle, P=2.5E-03; fourth ventricle, P=5.5E-03). Specifically, carriers of the G allele, which was reported as protective for ADHD, had a smaller increase of ventricular size compared with homozygotes for the A allele in elder stages. Post hoc analysis on the subset of individuals older than 70 years of age reinforced these results (lateral ventricles, P=7.3E-05). In addition, the rs4916723, and the rs281324 displayed nominal significant age-dependent effects in trajectories of the amygdala volume (P=1.4E-03), and caudate volume (P=1.8E-03), respectively. Conclusions: To the best of our knowledge, this is the first study suggesting the involvement of protective genetic variants for ADHD on prevention of brain atrophy during adulthood.
Language	English
Publishing date	2020-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2020.00574
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Article ; Online: Three Decades of Dementia Research: Insights from One Small Community of Indomitable Rotterdammers.

Wolters, Frank J / Adams, Hieab H H / Bos, Daniel / Licher, Silvan / Ikram, M Arfan

Journal of Alzheimer's disease : JAD

2018 Volume 64, Issue s1, Page(s) S145–S159

Abstract: The most commonly encountered opening sentence in scientific publications about dementia undoubtedly relates to the overwhelming burden of disease. Finding an effective preventive or therapeutic intervention against dementia has been considered the most ... ...

Abstract	The most commonly encountered opening sentence in scientific publications about dementia undoubtedly relates to the overwhelming burden of disease. Finding an effective preventive or therapeutic intervention against dementia has been considered the most important unmet need in contemporary medicine. While efforts on tackling this devastating disease have increased exponentially, it is difficult to imagine that in the 1980s and early-1990s, the disease did not feature prominently on any public health report. Yet, it was already then that epidemiologists recognized the growing societal burden of dementia and rationalized that dementia is not necessarily part of aging. Indeed, the conviction that dementia is pathologically distinct from aging led to various efforts in search of unravelling its risk factors and understanding its pre-clinical phase. Among the early pioneers, the population-based Rotterdam Study was initiated in 1990 clearly aiming on chronic diseases including dementia, and among this Alzheimer's disease, as one of its focus points. Ever since, the Rotterdam Study has been an important cornerstone in increasing our knowledge about dementia from an epidemiological perspective. Here, we summarize the main findings originating from this study, and put these into perspective with previous and current work in the field. With an expanding scope of the Rotterdam Study over the years, we discuss findings on occurrence, modifiable risk factors, imaging, and its genetic underpinnings. Importantly, we conclude with recommendations- or, perhaps better stated, a wish list- for future research which may help us reach our finish line: finding an effective preventive or therapeutic intervention against dementia.
MeSH term(s)	Animals ; Dementia/diagnostic imaging ; Dementia/epidemiology ; Dementia/genetics ; Dementia/therapy ; Humans ; Netherlands
Language	English
Publishing date	2018-05-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-179938
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Article: Genetic Influences on Hippocampal Subfields: An Emerging Area of Neuroscience Research.

Vilor-Tejedor, Natalia / Evans, Tavia E / Adams, Hieab H / González-de-Echávarri, José María / Molinuevo, José Luis / Guigo, Roderic / Gispert, Juan Domingo / Operto, Grégory

Neurology. Genetics

2021 Volume 7, Issue 3, Page(s) e591

Abstract: There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the ... ...

Abstract	There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the mechanisms of neurologic diseases, as well as aging and neurodegenerative processes. However, despite the emerging interest in this area of research, the current knowledge of the genetic architecture of hippocampal subfields has not yet been consolidated. We aimed to provide a review of the current evidence from genetic studies of hippocampal subfields, highlighting current priorities and upcoming challenges. The limited number of studies investigating the influential genetic effects on hippocampal subfields, a lack of replicated results and longitudinal designs, and modest sample sizes combined with insufficient standardization of protocols are identified as the most pressing challenges in this emerging area of research.
Language	English
Publishing date	2021-05-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000591
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Article ; Online: GenNet framework: interpretable deep learning for predicting phenotypes from genetic data.

van Hilten, Arno / Kushner, Steven A / Kayser, Manfred / Ikram, M Arfan / Adams, Hieab H H / Klaver, Caroline C W / Niessen, Wiro J / Roshchupkin, Gennady V

Communications biology

2021 Volume 4, Issue 1, Page(s) 1094

Abstract: Applying deep learning in population genomics is challenging because of computational issues and lack of interpretable models. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this ... ...

Abstract	Applying deep learning in population genomics is challenging because of computational issues and lack of interpretable models. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this framework, interpretable and memory-efficient neural network architectures are constructed by embedding biologically knowledge from public databases, resulting in neural networks that contain only biologically plausible connections. We applied the framework to seventeen phenotypes and found well-replicated genes such as HERC2 and OCA2 for hair and eye color, and novel genes such as ZNF773 and PCNT for schizophrenia. Additionally, the framework identified ubiquitin mediated proteolysis, endocrine system and viral infectious diseases as most predictive biological pathways for schizophrenia. GenNet is a freely available, end-to-end deep learning framework that allows researchers to develop and use interpretable neural networks to obtain novel insights into the genetic architecture of complex traits and diseases.
MeSH term(s)	Deep Learning ; Humans ; Neural Networks, Computer ; Phenotype
Language	English
Publishing date	2021-09-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02622-z
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